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Background: Colorectal cancer (CRC) is a common digestive tract malignancy with high incidence and mortality rates. Radiotherapy is the most common anti-tumor therapeutic regime and is frequently used for treating CRC, especially rectal cancer. However, radiotherapy can lead to tumor resistance to treatment. While previous research on radiotherapy resistance in CRC has mostly focused on the tumor itself, recent advances, especially the emergence of immunotherapy, have led to a greater emphasis on the immune microenvironment of the tumor. Summary: This review has summarized the recent literature on the role of the tumor immune microenvironment in CRC resistance to radiotherapy and provided new ideas for future anti-tumor treatment strategies. Key Messages: The proportion of immunosuppressive cells is greater than the numbers of cells associated with immune activation, leading to an overall state of immunosuppression; both the tumor and immunosuppressive cells secrete increased amounts of immunosuppressive regulatory factors, reduce the recognition and presentation of tumor antigens, inhibit immune cell's anti-tumor effect, and offset the non-targeted anti-tumor effect of radiotherapy. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a serious health problem and may lead to advanced liver cirrhosis and hepatocellular carcinoma if left untreated. In this study, a mouse liver fibrosis model was established by the administration of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and tanshinone IIA. Salvia miltiorrhiza Bunge extract, shown to play a regulatory role in liver fibrosis, was administered to study its effect on the expression of COL1A1. Mice were divided into 3 groups, control (Con), model (DDC), and drug administration (DDC-Tan) groups, and were subjected to the respective treatment for 2 months. Following treatment, the degree of liver fibrosis in mice in each group was determined. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and albumin levels in mice were determined using enzyme-linked immunosorbent assay (ELISA). Mouse liver tissues were used for hematoxylin-eosin and immunohistochemical staining. ELISA results showed that treatment with tanshinone IIA inhibited the expression of ALT, AST, and bilirubin in the DDC-Tan group compared with the DDC group. Hematoxylin-eosin, Sirius red, and α-SMA staining showed that liver injury was delayed in the DDC-Tan group. Immunohistochemistry, quantitative polymerase chain reaction, and Western blot results showed that COL1A1 expression was reduced after tanshinone IIA treatment. Moreover, the bioinformatic analysis indicated that let-7a targets COL1A1, and H19 regulates let-7a expression. The quantitative polymerase chain reaction and Western blot results confirmed that the H19/let-7a axis regulates COL1A1 expression. Thus, tanshinone IIA inhibited liver fibrosis by regulating COL1A1 expression through the H19/let-7a axis in mice. [ABSTRACT FROM AUTHOR]

Ginkgo biloba extract (GBE) has antitumor and antioxidant properties, which play a role in regulating gene and protein expression. The ten-eleven translocation (TET) proteins have the ability to regulate epigenetic modifications. However, the abnormal expression of TET2 protein has also been demonstrated in cancer development. In the present study, we analyzed the effects of GBE administration on TET2 expression in human colorectal cancer (CRC). The Cancer Genome Atlas database suggested that the expression of TET2 was lost in CRC. To investigate the expression profiles of TET2, GBE was used to treat CRC cells. The results showed that GBE could increase the expression of TET2 and 5-hydroxymethylcytosine (5hmC). In addition, GBE inhibited cell growth and invasion in SW480 cells. Moreover, to confirm whether TET2 expression affected cell proliferation, apoptosis, migration, and invasion, TET2 was knocked down and a TET2-overexpressing vector was constructed in human CRC cells. The results showed that overexpression of TET2 induced cell proliferation and invasion. Bioinformatic analyses showed that TET2 is a target gene of microRNA-29a (miR-29a). Moreover, reduced expression of miR-29a and increased TET2 expression in CRC cells. GBE was also used to treat a tumor model in nude mice. Compared to the control group, tumor growth was inhibited, and there was increased expression of TET2 in the GBE-treatment group in vivo. In conclusion, these results indicated that GBE inhibited cell proliferation and invasion through TET2 protein expression regulated by miR-29a in the development of CRC. [ABSTRACT FROM AUTHOR]

Gastric cancer and colorectal cancer are malignant tumors found in the human gastrointestinal tract. Bidirectional communication between tumor cells and their microenvironment can be realized through the transmission of exosomes—small, cell-derived vesicles containing complex RNA and proteins. Exosomes play an important role in the proliferation, metastasis, immune response, and drug resistance of cancer cells. In this review, we focus on the role and application of exosomes in gastric and colorectal cancer. We also summarize the role of exosomes secreted by different types of cells in tumor development and as drug carriers in cancer treatment. [ABSTRACT FROM AUTHOR]

Introduction: The expression of MiR-135b-5p was up-regulated while Krüppel-like factor 4 (KLF4) expression was extremely low in human gastric carcinoma (GC) tissues. This study aimed to explore the role of miR-135b-5p in GC cells and its influence on various cell capacity and viability by targeting KLF4.Material and Methods: The dual-luciferase reporter assay was first performed and the target relationship between miR-135b-5p and KLF4 was confirmed. Then three GC cell lines and the human normal gastric epithelial cell line (GES1) were analyzed for the expression level of miR-135b-5p and KLF4 mRNA by RT-qPCR. The BGC-823 GC cell line was chosen for subsequent assays.Results: The expression of miR-135b-5p and KLF4 was manipulated via transfection. The changes of proliferation, invasion, migration, viability, cycle and apoptosis of GC cells were evaluated by MTS, colony formation assay, transwell assay, wound healing assay and flow cytometry assay, respectively. Overexpression of MiR-135b-5p enhanced viability, proliferation, invasion and migration of GC cells, increased cell viability and reduced cell apoptosis. Replenishing of KLF4 functioned oppositely.Conclusions: The inhibitory effects of ectopic KLF4 could be attenuated by co-transfection of miR-135b-5p. Collective data suggested that miR-135b-5p has a tumor-promoting role in GC cells via downregulating KLF4. Hence, inhibition of miR-135b-5p could be valuable for treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Effect of Runx3 gene on the cell proliferation and invasion of rectal cancer was investigated to explore potential new targets for targeted treatment of rectal cancer. The Runx3 overexpression group (OE group), blank plasmid control group, negative control and blank group of the rectal cancer HRC-9698 cell strain were set. The overexpressed Runx3 plasmid was transfected in OE group; the empty plasmid was transfected in blank plasmid control group; only liposome Lipofectamine was added to negative control group; only 1640 medium was used in blank group. RT-qPCR was used for detection of the mRNA expression of Runx3 in different groups; CCK-8 kit for detection of cell proliferation in different groups; Transwell chamber test for detection of cell strain invasion in different groups. The mRNA expression of Runx3 gene in OE group was the highest, significantly higher than that in blank plasmid control group, negative control and blank group (P<0.01). The OD values of overexpressed Runx3 at 96 h after transfection in OE group was significantly lower than each control group (P<0.01). At the same time-point, pairwise comparison in each group found that OE group was significantly lower than blank plasmid control, negative control and blank groups (all P<0.01). In the invasion experiment, the number of invasion cells in OE, blank plasmid control, negative control and blank groups were 38.63±9.33, 107.87±5.66, 110.93±4.33 and 112.86±6.66, respectively. OE group was significantly lower than each control group (P<0.01). Overexpression of Runx3 gene in vitro inhibits the cell proliferation of rectal cancer and blocks the cell invasion and metastasis. This study provides a new idea and a new molecular therapeutic target for molecular targeted therapy of rectal cancer. [ABSTRACT FROM AUTHOR]

Summary: YWHAZ (14‐3‐3ζ) plays crucial roles in regulating proliferation, apoptosis, migration, and invasion of gastric cancer (GC) cells. However, its extensive roles and potential mechanisms in GC cells remain unknown, and need to be researched deeply. In this study, we focus on the role of miR‐375/YWHAZ axis in migration, invasion and epithelial‐to‐mesenchymal transition (EMT) of GC cells. YWHAZ level was assessed by western blot and qPCR assays in GC cells. Scratch and transwell assays were used to determine the migration and invasion of GC cells. The protein levels of correlative molecules were detected by western blot. The regulation of miR‐375 on the expression of its target gene YWHAZ was verified by dual‐luciferase report system. According to the results, knockdown of YWHAZ inhibited the migration, invasion and EMT of GC cells. Moreover, silencing of YWHAZ restrained the activation of wnt/β‐catenin signalling pathway. YWHAZ was confirmed to be a target gene of miR‐375, and its expression was regulated by miR‐375 in GC cells. Transfection of miR‐375 inhibitor promoted the migration, invasion, EMT and activation of wnt/β‐catenin pathway in GC cells, which was suppressed by inhibition of YWHAZ. Taken together, this study suggests that miR‐375/YWHAZ axis may be served as a novel therapeutic target for GC patients. [ABSTRACT FROM AUTHOR]

MicroRNA (miR)-613 has been reported to function as a tumor suppressor in several types of cancer. However, the biological function and underlying mechanism in gastric cancer (GC) has remained elusive. Therefore, the aim of the present study was to assess the expression and biological role of miR-613 in GC tissues and cell lines. miR-613 expression was found to be downregulated in 38 GC tissue samples compared to that in their adjacent non-cancerous tissues, and low expression of miR-613 was associated with lymph node metastasis and advanced tumor-nodes-metastasis stage. A gain-of-function assay demonstrated that miR-613 overexpression reduced tumor cell proliferation, migration and invasion of SGC-7901 cells, as determined by MTT and Transwell assays. Furthermore, brain-derived neutrophic factor (BDNF) was identified as a direct target of miR-613 in GC cells by a luciferase reporter assay. BDNF expression was upregulated and inversely correlated with miR-613 levels in GC tissues. In addition, knockdown of BDNF expression mimicked the tumor suppressive effect of miR-613 in GC cells. In conclusion, these findings demonstrated that miR-613 functions as a tumor suppressor in GC by targeting BDNF. Thus, miR-613 is a potential therapeutic target for GC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. Methotrexate (MTX) is one of the earliest cytotoxic drugs and serves as an anti-metabolite and anti-folate chemotherapy for various types of cancer. However, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the efficacy of MTX therapies in clinics. Long non-coding RNAs (lncRNAs) have gained widespread attention in recent years. More and more evidences have shown that lncRNAs play regulatory roles in various biological activities and disease progression including drug resistance in cancer cells. Here, we observed lncRNA TUG1 was associated to the MTX resistant in colorectal cancer cells. Firstly, quantitative analysis indicated that TUG1 was significantly increased in tumors which were resistant to MTX treatment. TUG1 knockdown re-sensitized the MTX resistance in colorectal cancer cells, which were MTX-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-186 could directly bind to TUG1, suggesting TUG1 might worked as a ceRNA to sponge miR-186. Extensively, our study also showed that CPEB2 was the direct target of miR-186 in colorectal cancer cells. Taken together, our study suggests that lncRNA TUG1 mediates MTX resistance in colorectal cancer via miR-186/CPEB2 axis. [ABSTRACT FROM AUTHOR]

Object: To compare the clinical efficacy of titanium mesh cages and autogenous iliac bone graft to restore vertebral height through posterior approach in patients with thoracic and lumbar spinal tuberculosis. Method: 59 patients with spinal tuberculosis underwent interbody fusion and internal fixation through posterior approach in our department from January 2011 to December 2013. In group A, 34 patients obtained titanium mesh for the reconstruction of vertebral height, among them 25 patients (group A1) suffered from single-segment spinal tuberculosis, and 9 patients, (group A2) had multi-segment spinal tuberculosis. In group B, 25 patients got autogenous iliac bone graft to restore vertebral height, including 24 patients with single-segment spinal tuberculosis (group B1), and 1 patient with multi-segment spinal tuberculosis (group B2). The clinical efficacy was evaluated based on average operation time, blood loss, hospital stays, hospitalization expenses, visual analog scale (VAS), Oswestry Disability Index (ODI), erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), neurological function recovery, bony fusion, intervertebral height, Cobb angle and postoperative complications. Results: Final follow-up time was an average of 35.5 months ranging from 15 to 56 months. All patients were completely cured and obtained solid bone fusion. The bony fusion time was 9.4±6.1 months in group A1, 10.2±2.7 months in group A2 and 8.7±3.6 months in group B1. There were no significant difference among three groups (P>0.05). The Cobb correction and restoration of intervertebral height significantly improved compared with those in preoperation, but without significant difference among three groups (P>0.05). The loss of angular correction and intervertebral height in group A1 were found to be less than those in group B1 (P<0.05), but with no significant difference between group A1 and group A2, and between group A2 and group B1 (P>0.05). Patients in group B1 got the most loss of angular correction and intervertebral height. In addition, neurological function was revealed to be significantly improved after surgery. There were significant differences of VAS, ODI, ESR and CRP between preoperation and postoperation at the final follow-up time (P<0.05), with no significant difference among three groups (P>0.05). No statistically significant difference was found when analyzing blood loss, hospital stays, hospitalization expenses, and corrective cost among three groups (P>0.05). Complications included cerebrospinal fluid leakage (2 cases in group A1 and group A2), sinus formation (3 cases in group A1, group A2 and group B1), and intervertebral infection (1 case in group B1), but no implant failure or donor site complications was found in any patient. Conclusions: Titanium mesh cages could obtain good clinical efficacy comparable to autogenous iliac bone graft when treating single-segment spinal tuberculosis, and may be better than autogenous iliac bone graft for treating multi-segment spinal tuberculosis. [ABSTRACT FROM AUTHOR]

Activating transcription factor 1 (ATF1) may be involved in essential hypertension (EH) by induction of NADPH oxidase 1 (NOX1) and radical oxygen species (ROSs) production. Abnormal expression of ATF1 was found in EH in previous microarray analysis. Here we tested whether a single nucleotide polymorphism (SNP) located in the 3′-untranslated region (3′UTR) of ATF1 was associated with EH susceptibility by affecting microRNA (miRNA) binding. In silico analysis indicated that rs11169571 (T > C) was a candidate SNP to modulate miRNA: ATF1 mRNA complex, with the greatest changed energy for hsa-miR-1283, and the luciferase reporter analysis showed that miR-1283 inhibited the activity of the reporter vector carrying –T allele, but not the –C allele. In addition, inhibition of miR-1283 in HA-VSMCs enhanced the expression of ATF1 mRNA as well as the ROS levels. Further case-control study showed that rs11169571 was significantly associated with increased risk of EH. Finally, we observed an increased ATF1 protein level in peripheral blood of EH patients with CC carriers compared to TT carriers of rs11169571, with an intermediate ATF1 level in TC carriers. These results suggested that rs11169571 of ATF1 gene may be associated with EH, and the SNP-modified posttranscriptional gene regulation by miRNAs could be a potentially pathogenetic mechanism of EH. [ABSTRACT FROM AUTHOR]

A cis-9-octadecenoic acid (OA) surface-modified TiO2 nanoparticle with average diameter of 30 nm was chemically synthesized. The tribological properties of the prepared OA–TiO2 nanoparticle as an additive in water were evaluated with a four-ball tester. The results show that the OA–TiO2 nanoparticle exhibits good antiwear and friction reduction properties as well as load-carrying capacity. The maximum non-seizure load (PB value) can be raised about 6–10 times when 0.1–1.0% OA–TiO2 nanoparticle was added into water. The rubbed surface after friction tests was investigated with X-ray photoelectron spectroscopy (XPS). The results of XPS analysis indicate that a boundary film mainly composed of TiO2 and oleic acid complex, was formed on the rubbed surface. [Copyright &y& Elsevier]

As the development of object detection technology in computer vision, identifying objects is always an active yet challenging task, and even more efficient and accurate requirements are being imposed on state-of-the-art algorithms. However, many algorithms perform object box regression based on RPN(Region Proposal Network) and anchors, which cannot accurately describe the shape information of the object. In this paper, we propose a new object detection method called Field Network (FN) and Region Fitting Algorithm (RFA). It can solve these problems by Center Field. Center field reflects the probability of the pixel approaching the object center. Different from the previous methods, we abandoned anchors and ROI technologies, and propose the concept of Field. Field is the intensity of the object area, reflecting the probability of the object in the area. Based on the distribution of the probability density of the object center in the visual field perception area, we add the Object Field in the output part. And we abstract it into an Elliptic Field with normal distribution and use RFA to fit objects. Additionally, we add two fields to predict the x,y components of the object direction which contain the neural units in the field array. We extract the objects through these Fields. Moreover, our model is relatively simple and have smaller size, which is only 73 M. Our method improves performance considerably over baseline systems on DOTA, MS COCO and PASCAL VOC datasets, with overall performance competitive with recent state-of-the-art systems. [ABSTRACT FROM AUTHOR]

3D pose estimation is always an active but challenging task for object detection in remote sensing images. In this paper, we present a new algorithm for predicting an object's 3D pose in remote sensing images, called Anchor Points Prediction (APP). Compared to previous methods, such as RoI Transform, our object results of the final output can obtain direction information. We predict the object's multiple feature points based on the neural network to obtain the homograph transformation relationship between object coordinates and image coordinates. The resulting 3D pose can accurately describe the three-dimensional position and attitude of the object. At the same time, we redefine the method I o U A P P for calculating the direction and posture of the object. We tested our algorithm on the HRSC2016 dataset and the DOTA dataset with accuracy rates of 0.863 and 0.701, respectively. The experimental results show that the accuracy of the APP algorithm is significantly improved. At the same time, the algorithm can achieve one-stage prediction, which makes the calculation process easier and more efficient. [ABSTRACT FROM AUTHOR]

The tribological properties of imidazoline borate at different concentration and different load in water were evaluated using a four-ball test machine. The tribological test results showed that the imidazoline borates have good load carrying capacity and lubrication property. The rubbed surfaces were investigated using X-ray photoelectron spectroscopy (XPS) and electron probe microanalyzer (EPMA). The results showed that imidazoline borates reacted with the metal surface in tribological process and produced a complex film, which is composed of organic imidazolines and partially decomposed products. [Copyright &y& Elsevier]

Endoplasmic reticulum aminopeptidase 1 (ERAP1) may be involved in blood pressure regulation by inactivation of angiotensin II and generation of bradykinin. Our previous study with cDNA microarray indicated that the expression of ERAP1 is down-regulated in essential hypertension (EH) patients. Since the 3′untranslated region (3′UTR) is known to play an important role in the post-transcriptional regulation by influencing the stability and translation process of mRNA, the present study aims to identify single nucleotide polymorphisms (SNPs) in the 3′UTR of ERAP1 gene in a case–control study among the Northeastern Han Chinese through PCR-sequencing, and analyze the association with EH. Our results further verified the lower expression level of ERAP1 in the peripheral blood cells in patients with EH (917.12 ± 517.57 vs. 1506.59 ± 1214.09 pg/mL, P = 0.011). Four SNPs, 3′UTR-761G>A, 3′UTR-787C>T, 3′UTR-1008A>C and 3′UTR-1055A>G, were identified in the 3′UTR of ERAP1 . 3′UTR-1008A>C and 3′UTR-1055A>G were in almost complete linkage disequilibrium. Association analysis showed that the genotypic and allelic frequencies of 3′UTR-1008A>C and 3′UTR-1055A>G were significantly different between EH and the control groups. Logistic regression and haplotypic analysis indicated that alleles of E20-1037C and E20-1084G as well as haplotype of C-G were the risk factors of EH (P < 0.05). Subgroup analysis performed by age suggested that the frequencies of genotype and allele of 3′UTR-1008A>C and 3′UTR-1055A>G as well as the haplotypes C-G and A-A were significantly different between EH and the control in the younger group (< 50), but not in the older group (≥ 50). Younger population with the 3′UTR-1008CC and/or 3′UTR-1055GG genotypes also tended to have higher blood pressure, especially the diastolic blood pressure. In conclusion, the 3′UTR-1008A>C and 3′UTR-1055A>G polymorphisms of ERAP1 gene were associated with EH, especially in the younger population, and the haplotype C-G could be the independent marker of EH. [ABSTRACT FROM AUTHOR]

Danggui-Jianzhong decoction (DGJZ) is a famous classical traditional Chinese medicine formula, which ingredients are complex and the quality is difficult to control. Our study aimed to identify the overall chemical profile of DGJZ qualitatively by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and UPLC. A total of 77 components, including terpenoids, flavonoids, phenolic acids, gingerols and other components, were firstly detected and characterized by UPLC-Q-TOF-MS and 18 peaks marked after analyzing the UPLC fingerprint. Finally, paeoniflorin, liquiritin, ferulic acid, cinnamic acid, glycyrrhizic acid and 6-gingerol were quantified, which was validated in terms of linearity, precision, accuracy, repeatability and recovery. Taken together, the chemical constitutes of DGJZ were systematically identified and a reliable quantitative method coupled with fingerprint analysis was successfully employed for evaluating the holistic quality, which will provide a robust foundation for the quality control of DGJZ., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Endometritis, a local inflammatory disease, has been known as the most common cause of infertility in mares. In this study, we investigated the protective effects of luteolin on endometritis induced by Staphylococcus aureus ( S. aureus ) and further clarified the possible molecular mechanisms. An S. aureus -induced endometritis model was established by the infusion of S. aureus into the uterus. Luteolin was intraperitoneally administered to mice 1 h before S. aureus treatment. The results showed that the mice of the S. aureus group showed severe histological changes of uterine tissues, increased myeloperoxidase (MPO) activity, and elevated TNF-α, IL-1β, and IL-6 levels. These changes induced by S. aureus were dose-dependently inhibited by luteolin. Furthermore, luteolin inhibited MDA and Fe 2+ production and increased the production of GSH decreased by S. aureus . Luteolin prevented S. aureus -induced endometrial barrier disruption through up-regulating ZO-1 and occludin expression. Luteolin dramatically inhibited S. aureus -induced NF-κB activation. The expression of Nrf2 and HO-1 was increased by luteolin. In addition, the inhibitory effects of luteolin on S. aureus -induced endometritis were reversed in Nrf2 knockdown mice. In conclusion, these data indicated that luteolin protected mice against S. aureus -induced endometritis through inhibiting inflammation and ferroptosis via regulating the Nrf2 signaling pathway.IMPORTANCEEndometritis is an inflammatory disease of the endometrium, which is a common gynecological disease. Up to now, there is no evidence for the protective effects of luteolin on endometritis. The purpose of this study was to investigate whether luteolin has protective effects against S. aureus -induced endometritis and attempts to clarify the mechanism., Competing Interests: The authors declare no conflict of interest.

Human hepatitis B virus (HBV) is a small enveloped DNA virus with a complex life cycle. It is the causative agent of acute and chronic hepatitis. HBV can resist immune system responses and often causes persistent chronic infections. HBV is the leading cause of liver cancer and cirrhosis. Interferons (IFNs) are cytokines with antiviral, immunomodulatory, and antitumor properties. IFNs are glycoproteins with a strong antiviral activity that plays an important role in adaptive and innate immune responses. They are classified into three categories (type I, II, and III) based on the structure of their cell-surface receptors. As an effective drug for controlling chronic viral infections, Type I IFNs are approved to be clinically used for the treatment of HBV infection. The therapeutic effect of interferon will be enhanced when combined with other drugs. IFNs play a biological function by inducing the expression of hundreds of IFN-stimulated genes (ISGs) in the host cells, which are responsible for the inhibiting of HBV replication, transcription, and other important processes. Animal models of HBV, such as chimpanzees, are also important tools for studying IFN treatment and ISG regulation. In the present review, we summarized the recent progress in IFN-HBV treatment and focused on its mechanism through the interaction between HBV and ISGs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Sun, Zhuo, Jiang, Li, Lin, Jin, Gao and Wang.)

Bile duct, pancreatic, and gastric cancers are deadly digestive system tumors with high malignancy and poor patient prognosis. The efficiencies of conventional surgical treatment, radiation therapy, and chemotherapy are limited. In contrast, chimeric antigen receptor (CAR) T-cell therapy represents a landmark therapeutic approach to antitumor immunity with great efficacy in treating several hematological malignancies. CAR T-cell therapy involves genetically engineering the expression of specific antibodies based on the patient's T-cell surface and amplifying these antibodies to identify and target tumor-associated antigens. CAR T-cell therapy can effectively inhibit disease progression and improve the survival of patients with bile duct, pancreatic, and gastric cancers. The effectiveness of CAR T cells in tumor therapy can be validated using xenograft models, providing a scientific testing platform. In this study, we have reviewed the progress in CAR T-cell production and its development, focusing on the current status and optimization strategies for engineered CAR T cells in the bile duct, pancreatic, and gastric cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Feng, Sun, Xue, Li, Lin, Gao, Sun, Zhuo and Wang.)

Collagen is a natural polymer expressed in the extracellular matrix of the peripheral nervous system. It has become increasingly crucial in peripheral nerve reconstruction as it was involved in regulating Schwann cell behaviors, maintaining peripheral nerve functions during peripheral nerve development, and being strongly upregulated after nerve injury to promote peripheral nerve regeneration. Moreover, its biological properties, such as low immunogenicity, excellent biocompatibility, and biodegradability make it a suitable biomaterial for peripheral nerve repair. Collagen provides a suitable microenvironment to support Schwann cells' growth, proliferation, and migration, thereby improving the regeneration and functional recovery of peripheral nerves. This review aims to summarize the characteristics of collagen as a biomaterial, analyze its role in peripheral nerve regeneration, and provide a detailed overview of the recent advances concerning the optimization of collagen nerve conduits in terms of physical properties and structure, as well as the application of the combination with the bioactive component in peripheral nerve regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Zhang, Hao, Wang, Jiang, Sun, Gao, Jin, Lei and Zhuo.)

More than 10% of the world's population already suffers from varying degrees of diabetes mellitus (DM), but there is still no cure for the disease. Cardiovascular disease (CVD) is one of the most common and dangerous of the many health complications that can be brought on by DM, and has become the leading cause of death in people with diabetes. While research on DM and associated CVD is advancing, the specific mechanisms of their development are still unclear. Given the threat of DM and CVD to humans, the search for new predictive markers and therapeutic ideas is imminent. Non-coding RNAs (ncRNAs) have been a popular subject of research in recent years. Although they do not encode proteins, they play an important role in living organisms, and they can cause disease when their expression is abnormal. Numerous studies have observed aberrant ncRNAs in patients with DM complications, suggesting that they may play an important role in the development of DM and CVD and could potentially act as biomarkers for diagnosis. There is additional evidence that treatment with existing drugs for DM, such as metformin, alters ncRNA expression levels, suggesting that regulation of ncRNA expression may be a key mechanism in future DM treatment. In this review, we assess the role of ncRNAs in the development of DM and CVD, as well as the evidence for ncRNAs as potential therapeutic targets, and make use of bioinformatics to analyze differential ncRNAs with potential functions in DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wang, Jiang, Gao, Sun, Li, Chen, Lin and Liu.)

Hepatocellular carcinoma (HCC) is a highly mortal type of primary liver cancer. Abnormal epigenetic modifications are present in HCC, and RNA modification is dynamic and reversible and is a key post-transcriptional regulator. With the in-depth study of post-transcriptional modifications, RNA modifications are aberrantly expressed in human cancers. Moreover, the regulators of RNA modifications can be used as potential targets for cancer therapy. In RNA modifications, N6-methyladenosine (m6A), N7-methylguanosine (m7G), and 5-methylcytosine (m5C) and their regulators have important regulatory roles in HCC progression and represent potential novel biomarkers for the confirmation of diagnosis and treatment of HCC. This review focuses on RNA modifications in HCC and the roles and mechanisms of m6A, m7G, m5C, N1-methyladenosine (m1A), N3-methylcytosine (m3C), and pseudouridine (ψ) on its development and maintenance. The potential therapeutic strategies of RNA modifications are elaborated for HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Feng, Wang, Xue, Lin, Gao, Sun, Jin and Liu.)

Colon adenocarcinoma (COAD) is one of the deadliest cancers in the world and survival rates vary significantly between early and advanced stage patients. Therefore, the identification of the pathogenesis in the development of COAD and prognostic markers is urgently demanded. Herein, we collected RNA-seq and somatic mutation data of COAD for statistical analysis. Clinical stage-specific differentially expressed genes (DEGs) and tumor development-dependent DEGs were identified. By characterizing the metabolic and immune features of COAD between stages, we found that the energy supply and inflammatory response of advanced tumors were suppressed. Next, the ETS1, AR, GATA1, GATA2, SREBF1, FOXP3, STAT4, and NFKB1 were identified to drive the metabolic and immune-related pathways in the development of COAD. The three potential prognostic markers ( HOXC8, IRF7, and CXCL13 ) were identified based on Cox regression analysis. Additionally, immune infiltration analysis revealed that the resting CD4 + T cell was significantly related to the overall survival (OS) of COAD patients. Collectively, the specific metabolic and immune characteristics of advanced patients and the identified prognostic biomarkers will contribute to the development of precision medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liao, Gao, Su and Feng.)

Extracellular vesicles (EVs) exert their biological functions by delivering proteins, metabolites, and nucleic acids to recipient cells. EVs play important roles in cancer development. The anti-tumor effect of EVs is by their cargos carrying proteins, metabolites, and nucleic acids to affect cell-to-cell communication. The characteristics of cell-to-cell communication can potentially be applied for the therapy of cancers, such as gastric cancer. In addition, EVs can be used as an effective cargos to deliver ncRNAs, peptides, and drugs, to target tumor tissues. In addition, EVs have the ability to regulate cell apoptosis, autophagy, proliferation, and migration of cancer cells. The ncRNA and peptides that were engaged with EVs were associated with cell signaling pathways in cancer development. This review focuses on the composition, cargo, function, mechanism, and application of EVs in cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Liu, Gao, Lin, An, Feng, Liu, Liu, Luo and Wang.)

Yupingfeng granules (YPFG) were isolated from a traditional Chinese medicine (TCM) formulation composed of three herbs (Astragali Radix, Atractylodis Macrocephalae Rhizoma, and Saposhnikoviae Radix). This formulation is used in TCM to tonify qi, and it can help strengthen exterior and reduce sweating. Nevertheless, the active components of YPFG remain unclear. In this study, the chemical constituents of YPFG were systematically characterized by ultra-performance liquid chromatography coupled with electrospray ionization/ quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS). Fifty-eight compounds, namely, 20 flavonoids, 19 saponins, nine organic acids, four volatile coumarins, three lactones, one alkaloid, and two other components, were identified. In addition, the constituents of YPFG with the potential for in vivo bioactivities following oral administration were investigated in Sprague-Dawley rats. Thirteen compounds, namely, 11 flavonoid-related and 2 saponin-related components, were detected in rat plasma. After enriching flavonoids and saponins in YPFG by extraction, the extracts and YPFG were administrated to immunosuppressed rats, respectively. Plasma samples were analyzed by UPLC-ESI-Q-TOF-MS, and principal component analysis (PCA) confirmed that the extracts had similar effects to YPFG. This method could discover active ingredients in YPFG quickly and provide a scientific basis for quality control and mechanism research., (© 2020 John Wiley & Sons, Ltd.)

Introduction: The expression of MiR-135b-5p was up-regulated while Krüppel-like factor 4 (KLF4) expression was extremely low in human gastric carcinoma (GC) tissues. This study aimed to explore the role of miR-135b-5p in GC cells and its influence on various cell capacity and viability by targeting KLF4., Material and Methods: The dual-luciferase reporter assay was first performed and the target relationship between miR-135b-5p and KLF4 was confirmed. Then three GC cell lines and the human normal gastric epithelial cell line (GES1) were analyzed for the expression level of miR-135b-5p and KLF4 mRNA by RT-qPCR. The BGC-823 GC cell line was chosen for subsequent assays., Results: The expression of miR-135b-5p and KLF4 was manipulated via transfection. The changes of proliferation, invasion, migration, viability, cycle and apoptosis of GC cells were evaluated by MTS, colony formation assay, transwell assay, wound healing assay and flow cytometry assay, respectively. Overexpression of MiR-135b-5p enhanced viability, proliferation, invasion and migration of GC cells, increased cell viability and reduced cell apoptosis. Replenishing of KLF4 functioned oppositely., Conclusions: The inhibitory effects of ectopic KLF4 could be attenuated by co-transfection of miR-135b-5p. Collective data suggested that miR-135b-5p has a tumor-promoting role in GC cells via downregulating KLF4. Hence, inhibition of miR-135b-5p could be valuable for treatment of gastric cancer., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)

The present study was performed to establish and characterize new human osteosarcoma cell lines resistant to pyropheophorbide-α methyl ester‑mediated photodynamic therapy (MPPa-PDT). MPPa-PDT-resistant cells are isolated from the human osteosarcoma MG63 and HOS cell lines and two resistant populations were finally acquired, including MG63/PDT and HOS/PDT. Cell Counting Kit-8 (CCK-8) assay was used to determine the MPPa-PDT, cisplatin (CDDP) resistance and proliferation of MG63, MG63/PDT, HOS and HOS/PDT cells. The intracellular ROS were analyzed using DCFH-DA staining. The colony formation, invasion and migration of parental and resistant cells were compared. FCM was employed to examine the cell cycle distribution, the apoptosis rate and the proportion of CD133+ cells. The fluorescence intensity of intracellular MPPa was observed by fluorescence microscopy and quantified using microplate reader. The protein levels were assessed by western blotting (WB). Compared with two parental cells, MG63/PDT and HOS/PDT were 1.67- and 1.61-fold resistant to MPPa-PDT, respectively, and also exhibited the resistance to CDDP. FCM assays confirmed that both MG63/PDT and HOS/PDT cells treated with MPPa-PDT displayed a significantly lower apoptosis rate in comparison with their corresponding parental cells. The expression of apoptosis-related proteins (i.e. cleaved-caspase 3 and cleaved‑PARP), intracellular ROS and the antioxidant proteins (HO-1 and SOD1) in MG63/PDT and HOS/PDT cells was also lower than that in parental cells. Both MG63/PDT and HOS/PDT cells exhibited changes in proliferation, photosensitizer absorption, colony formation, invasion, migration and the cell cycle distribution as compared to MG63 and HOS cells, respectively. Compared to MG63 and HOS cells, both resistant cell lines had a higher expression of CD133, survivin, Bcl-xL, Bcl-2, MRP1, MDR1 and ABCG2, but a lower expression of Bax. The present study successfully established two resistant human osteosarcoma cell lines which are valuable to explore the resistance-related mechanisms and the approaches to overcome resistance.

Recent reports suggest that colorectal carcinoma (CRC) may be sustained by a small subpopulation of cells, termed cancer stem cells (CSCs), which have drug resistance properties as a key reason for chemotherapy failure. The epidermal growth factor receptor (EGFR) controls CRC initiation and progression. Monoclonal antibody against EGFR (cetuximab) has been used in treatment of several cancers. However, the effects of cetuximab on CSCs in the CRC chemotherapy remain unclear. Here, we studied the effects of cetuximab on the CSC-like cells in Fluorouracil (5-FU)-treated CRC cells. CSC-like cells were independently isolated from CRC cells using CD133, CD44 or EphB2-high as markers and confirmed by tumor sphere formation assay. We found that 5-FU increased the apoptotic death of CSC-like CRC cells. Co-application of cetuximab augmented the apoptotic death of CSC-like CRC cells by 5-FU, seemingly through inhibition of 5-FU-induced increases in cell autophagy in CSC-like CRC cells. Together, our data suggest that EGFR monoclonal antibody may sensitize CSC-like CRC cells to 5-FU-induced apoptosis by affecting autophagy.